Growth hormone, produced in the pituitary gland, is one of the body’s three major anabolic hormones. The others are testosterone and insulin. A peptide hormone, meaning that it’s composed of a long chain of amino acids in a specific sequence, supplemental growth hormone must be administered by injection. As noted in a previous installment of this column, GH use by athletes and bodybuilders is rampant, mainly because it remains undetectable by current drug-testing methods. Whether using GH alone provides any true anabolic effects to athletes remains a matter of conjecture, although numerous anecdotes testify that it does. Bodybuilders rarely, if ever, use GH alone; it’s part of the anabolic hormone triumvirate, with testosterone and insulin.
The other population interested in GH is older. GH drops about 14 percent per decade, and some antiaging researchers suggest that the loss of GH and insulinlike growth factor 1 may be responsible for the loss of both physical and mental function common in older people. IGF-1 is produced in the liver under the stimulation of GH release. It’s also produced locally in muscle, where it’s involved in muscle repair and growth. Both hormones maintain muscle and connective tissue, and their lack may be involved in the loss of lean mass seen in the aged.
Some studies, notably a 2007 study published by researchers from Stanford University, examined the use of GH therapy in the aged and concluded that the risks outweighed any potential benefits. It was a meta-analysis, or compilation, of previous GH studies, most of which used excessive doses and produced such side effects as peripheral edema, which is water retention in the extremities, joint pain, muscle pain, glucose intolerance and loss of insulin sensitivity. The latter two effects can set people up for diabetes if they have the genetics for the disease. Although it wasn’t mentioned in the Stanford analysis, numerous recent studies show that much lower doses produce the benefits of GH minus the side effects.
Still, the fact that GH must be injected presents problems for many people. Injections don’t duplicate the hormone’s natural release pattern, which could be related to side effects. GH is normally released in small bursts, or pulses, several times a day, with the major pulse released during the initial 90 minutes of sleep, during stage-4, deep sleep. Because of the problem, researchers have sought other ways to boost sagging GH. Since GH is nothing more than a complex protein, though, taking it orally means it would just be broken down in the gut.
As research into the mysteries of GH continued, scientists discovered GH receptors in the body and that much smaller amino acid peptides could interact with them to stimulate GH. Those peptides are called secretagogues and usually consist of about six amino acids linked together. Researchers also discovered ghrelin, another natural GH secretagogue. With that information scientists developed drugs such as MK-677 that mimic the effects of ghrelin and other GH secretagogues in the body.
Secretagogue drugs offer considerable potential advantages over GH injections. For one, they can be taken orally with no loss of activity. They boost the natural pulsatile release of the body’s own GH. Although older people often have less GH, the pituitary continues to synthesize it throughout life. The problem is that other substances, such as somatostatin, that inhibit GH release also rise with age. GH release itself is governed by a balance between growth-hormone-releasing hormone and somatostatin. For unknown reasons, the body makes more somatostatin with age, while GHRH remains stable—an imbalance that favors somatostatin dominance and less GH release.
Oral GH secretagogues such as MK-677 bypass the somatostatin barrier by interacting directly with GH receptors, thus producing GH release. Since GH is quite expensive, an effective oral drug could replace GH injections and even eliminate most current GH-related side effects. The question is, Do the oral GH-releasing drugs work in the real world as well as they do on paper or in the lab?
A few studies show that GH secreatagogues such as MK-677 increase the body’s GH production in both the young and the old. In the most recent study that examined the effects of MK-677, 65 healthy people aged 60 to 81 received either 25 milligrams of MK-677 or a placebo for two years.1 During the first year some subjects got MK-677, while others got a placebo. After the first year those who had taken the placebo took actual MK-677, while those who had been taking the MK-677 either continued using the drug or were assigned to a placebo group. That’s known as a placebo-controlled, randomized, crossover double-blind study and is considered the highest quality study available.
As expected, the drug produced GH in amounts typical of young adults in the older people who used it, to the extent that 20 percent of lost lean mass was regained. Bodyfat increased on their arms and legs, which was surprising considering that GH is always linked to less bodyfat. While GH injections have been shown to decrease dangerous visceral bodyfat, MK-677 had no effect on that particular fat-storage area. Fasting blood glucose rose, while insulin sensitivity declined, which is common with GH injections. The most common side effect, however, was an increase in appetite that subsided in a few months. That’s no surprise, since MK-677 mimics the effects of ghrelin, which has a potent appetite-stimulating effect. Some subjects also experienced a mild lower-body edema and muscle pain. On the other hand, low-density lipoprotein declined in those on MK-677, an effect not produced by GH injections. A high count of LDL is linked to cardiovascular disease.
The authors note that MK-677 likely works because it mimics ghrelin in activating the body’s GH receptors. That system has a built-in safety factor because as GH rises, so does IGF-1. The increased IGF-1 signals the pituitary gland that the body has reached its optimal GH point. The pituitary responds by ceasing GH release. The increased fat stores in those on MK-677 reflect the ghrelin-like activity of the drug. While GH promotes fat oxidation, ghrelin promotes fat accretion. Although that doesn’t sound good, consider that many older people lose their appetite, which adds to the loss of muscle that frequently occurs. Unfortunately, MK-677 didn’t have any discernible effect on strength, function or quality of life in this study.
GH injections don’t increase strength in older people, however, or in younger people not deficient in the hormone. Only one study found an increase in strength in older men on GH, and they were also using testosterone. In this study, though, MK-677 did counteract three common factors related to muscle loss with age: reduced GH secretion, loss of fat-free mass and inadequate food intake.
Could GH secretagogues benefit those who are younger? Some preliminary studies show that giving MK-677 to young men boosts GH release and even encourages gains in lean mass. Secretagogues bypass the body’s usual limitations on GH release. On the other hand, using a drug that mimics ghrelin, such as MK-677, could reverse the effect of GH by causing hunger—and a considerable gain in bodyfat. I doubt that few bodybuilders would consider that an advantage.
GH secretagogues not based on ghrelin may be effective GH boosters without the negative body composition changes linked to a ghrelin-based drug. The primary advantage of such drugs, however, is to restore GH-releasing ability in older people at far less expense and in a more natural manner than in present GH replacement therapy.
GH Effects in Athletes: Real or Imagined?
Published research linking ergogenic effects to growth hormone use is scant. Yet its prevalence in bodybuilding and athletics cannot be denied. Surely GH does something to boost athletic prowess or muscle size and strength gains. Indeed, anecdotal evidence indicates that a combination of GH, testosterone and insulin is largely responsible for the noticeable difference in muscle mass between today’s bodybuilding competitors and those in the past. GH by itself isn’t very anabolic, but when it’s taken in that combination, the three hormones appear to offer a synergistic anabolic effect that hasn’t yet been explored or defined by mainstream science sources.
A recent study suggests that any gains made from using GH are entirely due to the placebo effect.2 Sixty-four noncompetitive recreational athletes were randomly assigned to either a placebo or GH group, the latter getting two milligrams a day of GH. The athletes didn’t know which group they were in. Physical performance was measured by various tests that examined endurance, strength, power and sprint capacity. More men than women believed they were receiving GH—81 percent vs. 31 percent. The men who thought they were taking GH improved both perceived and measured physical performance, even though they were in the placebo group. The authors suggest that many of the favorable effects ascribed to GH occur because athletes believe they will.
That isn’t unprecedented. More than 25 years ago a study was published in which powerlifters were told that they were getting injections of an anabolic steroid called Deca-Durabolin. About nine out of the 12 lifters reached their best lifts during the study. All the lifters had received placebo injections—which just goes to show that you can never discount the power of the placebo.
1 Nass, R., et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults. Ann Inter Med. 149:601-611.
2 Meinhardt, U., et al. (2008). The power of the mind: An evaluation of the placebo effect in a study of GH on physical performance. GH IGF-1 Res. 18(Supp): S34.
Editing errata: In the February ’09 installment of this column, “Testosterone and Rapid Weight Loss,” the statement, “The more SHBG your body has, the less testosterone you have in your blood,” should have read, “The more SHBG your body has, the less active testosterone you have in your blood.” Also, the statement, “In addition, the carbohydrate and fat may have spurred an increased release of growth hormone,” should have read, “In addition, the reduced carbohydrate and fat may have spurred an increased release of growth hormone.” IM